Under the command of recently-demoted Captain James Kirk, the ship was launched in 2286, after Kirk and crew saved Earth from an alien probe.

In 2287, the ship was soon called into service to address a hostage incident on Nimbus III. There, Enterprise was hijacked by the Vulcan zealot, Sybok, and taken to Sha Ka Ree, a planet beyond the Great Barrier that was supposedly home to God.

While in orbit of Sha Ka Ree, Enterprise was engaged by Captain Klaa and his Bird-of-Prey. Prior to escaping both the alien on the planet posing as "God" and his wrath, Enterprise fired a photon torpedo on the alien's location, thus buying time for Kirk, Spock and McCoy to escape.

In 2293, with some resistance from Kirk but at the urging of Spock, the ship was sent to escort Klingon Chancellor Gorkon to a peace conference on Earth. During the mission, Gorkon was assassinated, and the peace talks were called off.

Later, the Enterprise crew proved essential to the success of the rescheduled summit at Khitomer, by rescuing Kirk and McCoy from the penal colony, Rura Penthe, and defeating General Chang aboard his Bird-of-Prey that could fire while cloaked.

Following the events at Khitomer, the ship was scheduled for decommissioning.